B.R.S.M. The road to Tet. Lett. Is paved with good intentions

13Feb/144

Those hard to find references

In a recent group meeting the old Woodward aphorism came out again: "the only model system worth using is the enantiomer", which led to a scrabble afterwards to find when and where he'd actually said it. To my annoyance, I knew I'd undertaken the same search at the start of my PhD—and had all but given up until someone on Twitter helped me out. However, as I'd unfortunately lost the reference with the death of my old laptop, I again spent a considerable amount of time tracking it down again, for at least the second or third time in my life. Thus, as a favor to my future self—and in case anyone else is interested—I'm documenting the origins of the phrase here.

The quote itself most likely comes from a remark made by Woodward during a lecture he gave in London in 1968 on his progress towards the synthesis of vitamin B12. I'm probably not going  to do a Woodward Wednesdays post on the B12 synthesis any time soon for reasons of time (as much as anything), but to give some context to the quote, a partial retrosynthesis is shown below. Woodward disconnected the molecule into eastern (B/C) and western domains (A/D), and set out to synthesise the western domain from the tricyclic indoline shown. Although B12 would be a daunting molecule to synthesis even diastereoselectively today, Woodward's aim was in fact to devise a route to the target in its natural,  enantioenriched form—which in the 1960s meant either a dip in the chiral pool, or a resolution. Although the group was able to develop a route to either enantiomer of the slightly later intermediate XXXVII, starting from (+)- or (-)-camphor, for the final sequence they found that it was in fact more efficient to instead use a resolution of the earlier indoline, accomplished by derivatisation with (S)-α-phenylethyl isocyanate and separation of the resulting diastereomers.

B12

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